After winning the toss and batting in the third and final Test in Jamaica, Australia went to dinner on the first evening at 3-138 with Konstas out for 17 and Khawaja 23.
Cameron Green was also bowled for 46 before the second break, with Steve Smith 36no and Travis Head unbeaten on three on a day where selectors made the shock call to leave out Nathan Lyon.
Still, all eyes remain on Australia's top order, with Khawaja's 47 in the first Test in Barbados the only score from either opener above 25 in this Frank Worrell Trophy series.
The 38-year-old Khawaja fought through a torrid opening session on Saturday (Sunday AEDT), as the pink Dukes ball was moving and regularly beat the bat.
But the left-hander was superbly caught behind by Shai Hope on 23, edging a ball that was angled back in at him from around the wicket by Shamar Joseph.
Konstas had also shown signs of digging in, before being lbw for 17 after moving to an off-stump guard for this Test.
He at one stage faced 18 straight dot balls early, while surviving a run-out scare and edge to third slip on consecutive deliveries while on one.
Konstas threatened to find some rhythm when he hooked Alzarri Joseph's first ball for four and later punched the quick to the point boundary off the back foot.
But the 19-year-old fell lbw to Justin Greaves' first ball and his series average sits at just 10.Â
Khawaja's is 20.6, with one innings remaining in Australia's last Test before this summer's home Ashes.
Australia have battled with the opening spot since David Warner's retirement, after Smith's aborted move up the order last year and Nathan McSweeney's three Tests last summer.
Marnus Labuschagne also opened in the World Test Championship final loss to South Africa, for scores of 17 and 22 before being dropped.
The other chief talking point of Saturday was the omission of Lyon, with Scott Boland coming in for the day-night Test.
Lyon has played every Test he has been fit for since the second Test of the 2013 Ashes, racking up 100 consecutive matches after that.
The spinner then suffered a calf tear at Lord's in 2023 and missed the final three Tests of that Ashes, before returning to the side for the start of the next summer.
While the day-night Tests are generally thought to suit the quicks under lights, Lyon has a better record with pink balls than red.
This Test is being played with a Dukes ball rather than a Kookaburra, with the Windies' two tweakers finding some turn.
Lyon has had strong returns of nine wickets at 18.33 in a series dominated by quicks, but bowled only 32.3 overs across two Tests.
West Indies also made a big call, dropping out-of-form ex-captain Kraigg Brathwaite, ending his run of 90 straight Tests.
14°C